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Carla Maldonado - One of the best experts on this subject based on the ideXlab platform.
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historical chemical annotations of Cinchona Bark collections are comparable to results from current day high pressure liquid chromatography technologies
Journal of Ethnopharmacology, 2020Co-Authors: Nataly Allasi Canales, Claus Cornett, Carla Maldonado, Tobias Nikolaj Gress Hansen, Kim Walker, Felix Driver, Alexandre Antonelli, Mark NesbittAbstract:Abstract Ethnopharmacological relevance Species of the genus Cinchona (Rubiaceae) have been used in traditional medicine, and as a source for quinine since its discovery as an effective medicine against malaria in the 17th century. Despite being the sole cure of malaria for almost 350 years, little is known about the chemical diversity between and within species of the antimalarial alkaloids found in the Bark. Extensive historical Cinchona Bark collections housed at the Royal Botanic Gardens, Kew, UK, and in other museums may shed new light on the alkaloid chemistry of the Cinchona genus and the history of the quest for the most effective Cinchona Barks. Aim of the study We used High-Pressure Liquid Chromatography (HPLC) coupled with fluorescence detection (FLD) to reanalyze a set of Cinchona Barks originally annotated for the four major quinine alkaloids by John Eliot Howard and others more than 150 years ago. Materials and methods We performed an archival search on the Cinchona Bark collections in the Economic Botany Collection housed in Kew, focusing on those with historical alkaloid content information. Then, we performed HPLC analysis of the Bark samples to separate and quantify the four major quinine alkaloids and the total alkaloid content using fluorescence detection. Correlations between historic and current annotations were calculated using Spearman's rank correlation coefficient, before paired comparisons were performed using Wilcox rank sum tests. The effects of source were explored using generalized linear modelling (GLM), before the significance of each parameter in predicting alkaloid concentrations were assessed using chi-square tests as likelihood ratio testing (LRT) models. Results The total alkaloid content estimation obtained by our HPLC analysis was comparatively similar to the historical chemical annotations made by Howard. Additionally, the quantity of two of the major alkaloids, quinine and cinchonine, and the total content of the four alkaloids obtained were significantly similar between the historical and current day analysis using linear regression. Conclusions This study demonstrates that the historical chemical analysis by Howard and current day HPLC alkaloid content estimations are comparable. Current day HPLC analysis thus provide a realistic estimate of the alkaloid contents in the historical Bark samples at the time of sampling more than 150 years ago. Museum collections provide a powerful but underused source of material for understanding early use and collecting history as well as for comparative analyses with current day samples.
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phylogeny predicts the quantity of antimalarial alkaloids within the iconic yellow Cinchona Bark rubiaceae Cinchona calisaya
Frontiers in Plant Science, 2017Co-Authors: Carla Maldonado, Steen Honore Hansen, Else Holmfred, Claus Cornett, Alexandre Antonelli, Christopher Barnes, Claes Persson, Nina RonstedAbstract:Considerable inter- and intraspecific variation with respect to the quantity and composition of plant natural products exists. The processes that drive this variation remain largely unknown. Understanding which factors determine chemical diversity has the potential to shed light on plant defenses against herbivores and diseases and accelerate drug discovery. For centuries, Cinchona alkaloids were the primary treatment of malaria. Using Cinchona calisaya as a model, we generated genetic profiles of leaf samples from four plastid (trnL-F, matK, rps16, and ndhF) and one nuclear (ITS) DNA regions from twenty-two C. calisaya stands sampled in the Yungas region of Bolivia. Climatic and soil parameters were characterized and Bark samples were analyzed for content of the four major alkaloids using HPLC-UV to explore the utility of evolutionary history (phylogeny) in determining variation within species of these compounds under natural conditions. A significant phylogenetic signal was found for the content of two out of four major Cinchona alkaloids (quinine and cinchonidine) and their total content. Climatic parameters, primarily driven by changing altitude, predicted 20.2% of the overall alkaloid variation, and geographical separation accounted for a further 9.7%. A clade of high alkaloid producing trees was identified that spanned a narrow range of altitudes, from 1,100 to 1,350 m. However, climate expressed by altitude was not a significant driver when accounting for phylogeny, suggesting that the chemical diversity is primarily driven by phylogeny. Comparisons of the relative effects of both environmental and genetic variability in determining plant chemical diversity have scarcely been performed at the genotypic level. In this study we demonstrate there is an essential need to do so if the extensive genotypic variation in plant biochemistry is to be fully understood.
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an efficient robust and inexpensive grinding device for herbal samples like Cinchona Bark
Scientia Pharmaceutica, 2015Co-Authors: Steen Honore Hansen, Else Holmfred, Claus Cornett, Carla Maldonado, Nina RonstedAbstract:An effective, robust, and inexpensive grinding device for the grinding of herb samples like Bark and roots was developed by rebuilding a commercially available coffee grinder. The grinder was constructed to be able to provide various particle sizes, to be easy to clean, and to have a minimum of dead volume. The recovery of the sample when grinding as little as 50 mg of crude Cinchona Bark was about 60%. Grinding is performed in seconds with no rise in temperature, and the grinder is easily disassembled to be cleaned. The influence of the particle size of the obtained powders on the recovery of analytes in extracts of Cinchona Bark was investigated using HPLC.
Hanns Hatt - One of the best experts on this subject based on the ideXlab platform.
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Effects of Quinine, Quinidine and Chloroquine on Human Muscle Nicotinic Acetylcholine Receptors
Frontiers Media S.A., 2018Co-Authors: Günter Gisselmann, Desiree Alisch, Brigitte Welbers-joop, Hanns HattAbstract:The genus Cinchona is known for a range of alkaloids, such as quinine, quinidine, cinchonine, and cinchonidine. Cinchona Bark has been used as an antimalarial agent for more than 400 years. Quinine was first isolated in 1820 and is still acknowledged in the therapy of chloroquine-resistant falciparum malaria; in lower dosage quinine has been used as treatment for leg cramps since the 1940s. Here we report the effects of the quinoline derivatives quinine, quinidine, and chloroquine on human adult and fetal muscle nicotinic acetylcholine receptors (nAChRs). It could be demonstrated that the compounds blocked acetylcholine (ACh)-evoked responses in Xenopus laevis oocytes expressing the adult nAChR composed of αβδ subunits in a concentration-dependent manner, with a ranked potency of quinine (IC50 = 1.70 μM), chloroquine (IC50 = 2.22 μM) and quinidine (IC50 = 3.96 μM). At the fetal nAChR composed of αβγδ subunits, the IC50 for quinine was found to be 2.30 μM. The efficacy of the block by quinine was independent of the ACh concentration. Therefore, quinine is proposed to inhibit ACh-evoked currents in a non-competitive manner. The present results add to the pharmacological characterization of muscle nAChRs and indicate that quinine is effective at the muscular nAChRs close to therapeutic blood concentrations required for the therapy and prophylaxis of nocturnal leg cramps, suggesting that the clinically proven efficacy of quinine could be based on targeting nAChRs
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Data_Sheet_1_Effects of Quinine, Quinidine and Chloroquine on Human Muscle Nicotinic Acetylcholine Receptors.PDF
2018Co-Authors: Günter Gisselmann, Desiree Alisch, Brigitte Welbers-joop, Hanns HattAbstract:The genus Cinchona is known for a range of alkaloids, such as quinine, quinidine, cinchonine, and cinchonidine. Cinchona Bark has been used as an antimalarial agent for more than 400 years. Quinine was first isolated in 1820 and is still acknowledged in the therapy of chloroquine-resistant falciparum malaria; in lower dosage quinine has been used as treatment for leg cramps since the 1940s. Here we report the effects of the quinoline derivatives quinine, quinidine, and chloroquine on human adult and fetal muscle nicotinic acetylcholine receptors (nAChRs). It could be demonstrated that the compounds blocked acetylcholine (ACh)-evoked responses in Xenopus laevis oocytes expressing the adult nAChR composed of αβδ subunits in a concentration-dependent manner, with a ranked potency of quinine (IC50 = 1.70 μM), chloroquine (IC50 = 2.22 μM) and quinidine (IC50 = 3.96 μM). At the fetal nAChR composed of αβγδ subunits, the IC50 for quinine was found to be 2.30 μM. The efficacy of the block by quinine was independent of the ACh concentration. Therefore, quinine is proposed to inhibit ACh-evoked currents in a non-competitive manner. The present results add to the pharmacological characterization of muscle nAChRs and indicate that quinine is effective at the muscular nAChRs close to therapeutic blood concentrations required for the therapy and prophylaxis of nocturnal leg cramps, suggesting that the clinically proven efficacy of quinine could be based on targeting nAChRs.
Rueda Enciso, José Eduardo - One of the best experts on this subject based on the ideXlab platform.
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La administración liberal en la Provincia de Bogotá 1849-1857
2010Co-Authors: Rueda Enciso, José EduardoAbstract:Between 1849 and 1886, the first New Granada, after Confederation and later the United States of Colombia was the liberal republic in which free trade, federalism, the payment of direct taxes, regulation and collection of land registration, the organization of a police and the professionalization of the army, the separation of church and state, freedom of worship and public school secularization dominated the public discussion, political action and militant liberals and conservatives. Cundinamarca, as the seat of central government and a region mainly populated during the conquest and colonization in the highlands, but in the Nineteenth Century to colonize their interest and warm temperate zones, was the scene of a particular regional development, marked by navigation on the Magdalena River, the development of roadways and railways, the increase and collapse of an extractive economy centered on the Cinchona Bark, the tobacco, indigo and finally coffee, leading to an administration, governance and consistent policy, most times with the interests of the elites living in Bogota, sometimes in less amount, in the opposite.Entre 1849 y 1886, la primero Nueva Granada, luego Confederación neogranadina y posteriormente Estados Unidos de Colombia vivió la república liberal, en la que el libre cambio, el federalismo, el pago del impuesto directo, la reglamentación y cobro del catastro, la organización de un cuerpo de policía y la profesionalización del ejercito, la separación entre la Iglesia y el Estado, la libertad de cultos y la laicalización de la escuela pública dominaron el debate público, el accionar político y de los militantes de los liberales y los conservadores. Cundinamarca, por ser la sede del Estado central y ser una región mayoritariamente poblada durante la conquista y la colonia en el altiplano, pero en el siglo XIX interesada en colonizar sus zonas templadas y cálidas, fue escenario de un particular desarrollo regional, marcado por la navegación por el río Magdalena, el desarrollo de las vías de comunicación terrestres y férreas, los auges y caídas de una economía extractiva centrada en la quina, el tabaco, el añil y finalmente del café, lo que determinó una administración, un gobierno y una política acorde, la mayoría de veces, con los intereses de las elites residentes en Bogotá, otras, en menos cuantía, en contravía
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La administración liberal en la Provincia de Bogotá 1849-1857
'Universidad Industrial de Santander', 2010Co-Authors: Rueda Enciso, José EduardoAbstract:Between 1849 and 1886, the first New Granada, after Confederation and later the United States of Colombia was the liberal republic in which free trade, federalism, the payment of direct taxes, regulation and collection of land registration, the organization of a police and the professionalization of the army, the separation of church and state, freedom of worship and public school secularization dominated the public discussion, political action and militant liberals and conservatives. Cundinamarca, as the seat of central government and a region mainly populated during the conquest and colonization in the highlands, but in the Nineteenth Century to colonize their interest and warm temperate zones, was the scene of a particular regional development, marked by navigation on the Magdalena River, the development of roadways and railways, the increase and collapse of an extractive economy centered on the Cinchona Bark, the tobacco, indigo and finally coffee, leading to an administration, governance and consistent policy, most times with the interests of the elites living in Bogota, sometimes in less amount, in the opposite.Keywords: liberalism, administration, Province of Bogota, government, chamber provincial, elections, national guard and local.Entre 1849 y 1886, la primero Nueva Granada, luego Confederación neogranadina y posteriormente Estados Unidos de Colombia vivió la república liberal, en la que el libre cambio, el federalismo, el pago del impuesto directo, la reglamentación y cobro del catastro, la organización de un cuerpo de policía y la profesionalización del ejercito, la separación entre la Iglesia y el Estado, la libertad de cultos y la laicalización de la escuela pública dominaron el debate público, el accionar político y de los militantes de los liberales y los conservadores. Cundinamarca, por ser la sede del Estado central y ser una región mayoritariamente poblada durante la conquista y la colonia en el altiplano, pero en el siglo XIX interesada en colonizar sus zonas templadas y cálidas, fue escenario de un particular desarrollo regional, marcado por la navegación por el río Magdalena, el desarrollo de las vías de comunicación terrestres y férreas, los auges y caídas de una economía extractiva centrada en la quina, el tabaco, el añil y finalmente del café, lo que determinó una administración, un gobierno y una política acorde, la mayoría de veces, con los intereses de las elites residentes en Bogotá, otras, en menos cuantía, en contravía.Palabras clave: liberalismo, administración, provincia de Bogotá, gobernación, cámara provincial, elecciones, guardia nacional y local.
Mark Nesbitt - One of the best experts on this subject based on the ideXlab platform.
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historical chemical annotations of Cinchona Bark collections are comparable to results from current day high pressure liquid chromatography technologies
Journal of Ethnopharmacology, 2020Co-Authors: Nataly Allasi Canales, Claus Cornett, Carla Maldonado, Tobias Nikolaj Gress Hansen, Kim Walker, Felix Driver, Alexandre Antonelli, Mark NesbittAbstract:Abstract Ethnopharmacological relevance Species of the genus Cinchona (Rubiaceae) have been used in traditional medicine, and as a source for quinine since its discovery as an effective medicine against malaria in the 17th century. Despite being the sole cure of malaria for almost 350 years, little is known about the chemical diversity between and within species of the antimalarial alkaloids found in the Bark. Extensive historical Cinchona Bark collections housed at the Royal Botanic Gardens, Kew, UK, and in other museums may shed new light on the alkaloid chemistry of the Cinchona genus and the history of the quest for the most effective Cinchona Barks. Aim of the study We used High-Pressure Liquid Chromatography (HPLC) coupled with fluorescence detection (FLD) to reanalyze a set of Cinchona Barks originally annotated for the four major quinine alkaloids by John Eliot Howard and others more than 150 years ago. Materials and methods We performed an archival search on the Cinchona Bark collections in the Economic Botany Collection housed in Kew, focusing on those with historical alkaloid content information. Then, we performed HPLC analysis of the Bark samples to separate and quantify the four major quinine alkaloids and the total alkaloid content using fluorescence detection. Correlations between historic and current annotations were calculated using Spearman's rank correlation coefficient, before paired comparisons were performed using Wilcox rank sum tests. The effects of source were explored using generalized linear modelling (GLM), before the significance of each parameter in predicting alkaloid concentrations were assessed using chi-square tests as likelihood ratio testing (LRT) models. Results The total alkaloid content estimation obtained by our HPLC analysis was comparatively similar to the historical chemical annotations made by Howard. Additionally, the quantity of two of the major alkaloids, quinine and cinchonine, and the total content of the four alkaloids obtained were significantly similar between the historical and current day analysis using linear regression. Conclusions This study demonstrates that the historical chemical analysis by Howard and current day HPLC alkaloid content estimations are comparable. Current day HPLC analysis thus provide a realistic estimate of the alkaloid contents in the historical Bark samples at the time of sampling more than 150 years ago. Museum collections provide a powerful but underused source of material for understanding early use and collecting history as well as for comparative analyses with current day samples.
Alexandre Antonelli - One of the best experts on this subject based on the ideXlab platform.
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historical chemical annotations of Cinchona Bark collections are comparable to results from current day high pressure liquid chromatography technologies
Journal of Ethnopharmacology, 2020Co-Authors: Nataly Allasi Canales, Claus Cornett, Carla Maldonado, Tobias Nikolaj Gress Hansen, Kim Walker, Felix Driver, Alexandre Antonelli, Mark NesbittAbstract:Abstract Ethnopharmacological relevance Species of the genus Cinchona (Rubiaceae) have been used in traditional medicine, and as a source for quinine since its discovery as an effective medicine against malaria in the 17th century. Despite being the sole cure of malaria for almost 350 years, little is known about the chemical diversity between and within species of the antimalarial alkaloids found in the Bark. Extensive historical Cinchona Bark collections housed at the Royal Botanic Gardens, Kew, UK, and in other museums may shed new light on the alkaloid chemistry of the Cinchona genus and the history of the quest for the most effective Cinchona Barks. Aim of the study We used High-Pressure Liquid Chromatography (HPLC) coupled with fluorescence detection (FLD) to reanalyze a set of Cinchona Barks originally annotated for the four major quinine alkaloids by John Eliot Howard and others more than 150 years ago. Materials and methods We performed an archival search on the Cinchona Bark collections in the Economic Botany Collection housed in Kew, focusing on those with historical alkaloid content information. Then, we performed HPLC analysis of the Bark samples to separate and quantify the four major quinine alkaloids and the total alkaloid content using fluorescence detection. Correlations between historic and current annotations were calculated using Spearman's rank correlation coefficient, before paired comparisons were performed using Wilcox rank sum tests. The effects of source were explored using generalized linear modelling (GLM), before the significance of each parameter in predicting alkaloid concentrations were assessed using chi-square tests as likelihood ratio testing (LRT) models. Results The total alkaloid content estimation obtained by our HPLC analysis was comparatively similar to the historical chemical annotations made by Howard. Additionally, the quantity of two of the major alkaloids, quinine and cinchonine, and the total content of the four alkaloids obtained were significantly similar between the historical and current day analysis using linear regression. Conclusions This study demonstrates that the historical chemical analysis by Howard and current day HPLC alkaloid content estimations are comparable. Current day HPLC analysis thus provide a realistic estimate of the alkaloid contents in the historical Bark samples at the time of sampling more than 150 years ago. Museum collections provide a powerful but underused source of material for understanding early use and collecting history as well as for comparative analyses with current day samples.
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phylogeny predicts the quantity of antimalarial alkaloids within the iconic yellow Cinchona Bark rubiaceae Cinchona calisaya
Frontiers in Plant Science, 2017Co-Authors: Carla Maldonado, Steen Honore Hansen, Else Holmfred, Claus Cornett, Alexandre Antonelli, Christopher Barnes, Claes Persson, Nina RonstedAbstract:Considerable inter- and intraspecific variation with respect to the quantity and composition of plant natural products exists. The processes that drive this variation remain largely unknown. Understanding which factors determine chemical diversity has the potential to shed light on plant defenses against herbivores and diseases and accelerate drug discovery. For centuries, Cinchona alkaloids were the primary treatment of malaria. Using Cinchona calisaya as a model, we generated genetic profiles of leaf samples from four plastid (trnL-F, matK, rps16, and ndhF) and one nuclear (ITS) DNA regions from twenty-two C. calisaya stands sampled in the Yungas region of Bolivia. Climatic and soil parameters were characterized and Bark samples were analyzed for content of the four major alkaloids using HPLC-UV to explore the utility of evolutionary history (phylogeny) in determining variation within species of these compounds under natural conditions. A significant phylogenetic signal was found for the content of two out of four major Cinchona alkaloids (quinine and cinchonidine) and their total content. Climatic parameters, primarily driven by changing altitude, predicted 20.2% of the overall alkaloid variation, and geographical separation accounted for a further 9.7%. A clade of high alkaloid producing trees was identified that spanned a narrow range of altitudes, from 1,100 to 1,350 m. However, climate expressed by altitude was not a significant driver when accounting for phylogeny, suggesting that the chemical diversity is primarily driven by phylogeny. Comparisons of the relative effects of both environmental and genetic variability in determining plant chemical diversity have scarcely been performed at the genotypic level. In this study we demonstrate there is an essential need to do so if the extensive genotypic variation in plant biochemistry is to be fully understood.